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Breast Cancer Triple Negative Breast Cancer Pathological Diagnosis and Current Chemotherapy Treatment Options Bernardo L Rapoport, 1 Simon Nayler, 2 Georgia S Demetriou, 3 Shun D Moodley 4 and Carol A Benn 5 1. Specialist Physician and Medical Oncologist, The Medical Oncology Center of Rosebank, Johannesburg, South Africa; 2. Specialist Histopathologist, Gritzman and Thatcher Inc. and Wits Donald Gordon Medical Center, Johannesburg, South Africa; 3. Specialist Physician and Medical Oncologist, Department of Internal Medicine Division of Medical Oncology, University of the Witwatersrand and Wits Donald Gordon Medical Center, Johannesburg, South Africa; 4. Specialist Physician and Medical Oncologist, University of the Witwatersrand and Wits Donald Gordon Medical Center, Johannesburg, South Africa; 5. Specialist Surgeon, Netcare Milpark Hospital Breast Centre and Helen Joseph Hospital, University of the Witwatersrand, Johannesburg, South Africa Abstract Triple negative breast cancer (TNBC) comprises 12–20 % of all breast cancers and are a heterogeneous group of tumours, both clinically and pathologically. These cancers are characterised by the lack of expression of the hormone receptors oestrogen receptor (OR) and progesterone receptor (PR), combined with the lack of either overexpression or amplification of the human epidermal growth factor receptor-2 (HER2) gene. Conventional cytotoxic chemotherapy and DNA damaging agents continue to be the mainstay of treatment of this disease in the neoadjuvant, adjuvant and metastatic setting. The lack of predictive markers in identifying potential targets for the treatment of TNBC has left a gap in directed therapy in these patients. Platinum agents have seen renewed interest in TNBC based on an increasing body of preclinical and clinical data suggesting encouraging activity. However, comparisons between chemotherapy regimens are mostly retrospective in nature and the best agents or drug combinations for TNBC have not been established in prospective randomised trials. Numerous studies have now shown that TNBC has significantly higher pathological complete response (pCR) rates compared with hormone receptor positive breast cancer when treated with neoadjuvant chemotherapy, and pCR correlates well with better outcomes for these patients. Patients with TNBC account for a larger number of deaths in the setting of metastatic breast cancer. There is no preferred treatment for the first-line metastatic setting. Although individual agents are recommended, given the often aggressive nature of TNBC and the presence of extensive visceral disease, the use of a combination of drugs, rather than a single agent, is often advocated. This review article will outline the pathological diagnosis of TNBC and the treatment options available to these patients in the neoadjuvant, adjuvant and metastatic setting, including an assessment of future directions of treatment. Keywords Breast cancer, triple negative, pathological diagnosis, chemotherapy treatment, neoadjuvant, targeted treatment, adjuvant, metastatic Disclosure: Bernardo L Rapoport, Simon Naylor, Georgia S Demetriou, Shun D Moodley and Carol A Benn have no conflicts of interests to declare. No funding was received for the publication of this article. Received: 20 January 2014 Accepted: 30 March 2014 Citation: European Oncology & Haematology, 2014;10(1):35–42 Correspondence: Bernardo L Rapoport, The Medical Oncology Centre of Rosebank, 129 Oxford Road, Saxonwold 2196, Johannesburg, PO Box 2040, Parklands 2121, South Africa. E: brapoport@icon.co.za The treatment of triple negative breast cancer (TNBC) is an unmet medical need, which refers to tumours that are oestrogen receptor (OR) and progesterone receptor (PR) negative, and where human epidermal growth factor receptor 2 (HER2) is not overexpressed. This subset accounts for approximately 12–20 % of breast cancer patients. 1 Gene expression analysis on this heterogenous group of patients demonstrates an overlap between the molecular signature of TNBC and basal-like (BL) breast cancer (BLBC). The concordance rates between the two groups are in the order of 70–90 %. Not all TNBC can be defined as BLBC as a small minority of BLBC patients express OR and HER2 receptors. The purpose of this review is to discuss the pathological diagnosis, current trends in management of TNBC in the neo-adjuvant, adjuvant, and metastatic disease treatment and future directions. © TO U CH MED I CA L MED IA 2014 Pathological Features and Diagnosis of Triple Negative Breast Cancer TNBC, which comprises 12–20  % of all breast cancers, are a heterogeneous group of tumours, clinically and pathologically at the molecular level. 1 The defining features of this cohort of breast cancers are a lack of expression of the hormone receptors OR and PR, combined with a lack of either overexpression or amplification of the HER2 gene. The majority (around 70 %) has been demonstrated to be BLBC, and this subtype is defined by an overexpression of epidermal growth factor receptor-1 (EGFR-1) and basal cytokeratins, particularly the cytokeratin 5/6 (CK5/6), as well as cytokeratins 14 and 17. These pathological basal cell type TNBCs have a typical histopathological appearance, most being poorly differentiated grade 3 carcinomas, with some or all of the following microscopic features: solid growth pattern, a prominent lympho- plasmacytic infiltrate and a medullary-like growth pattern. The tumour 35